WASHINGTON, DC — Results of studies investigating the NeuroPace RNS System appear to support the long-term safety and effectiveness of this novel implantable device out to 6 years in open-label follow-up.
"We believe this represents an entirely new approach" to treating patients with epilepsy, said Martha J. Morrell, MD, chief medical officer at NeuroPace, the device manufacturer.
The NeuroPace system received US Food and Drug Administration (FDA) approval earlier this month. It's the first device to be approved for the treatment of epilepsy since 1997, Dr. Morrell told a press briefing here during the American Epilepsy Society (AES) 67th Annual Meeting.
The device is indicated for use as an adjunct treatment for adults with frequent, disabling, partial-onset seizures who have not responded to 2 or more antiepileptic drugs (AEDs).
The curved programmable device, which is not much bigger than a matchbox, is implanted into the skull, discreetly positioned above the ear — a major plus for some epileptic patients who feel stigmatized, said Dr. Morrell. "Patients can run their hands over their scalp and won't feel it and it can't be seen," she said.
The device is attached to 2 leads, each with 4 electrodes that are placed at the location of the seizure focus. When the device detects abnormal electrical activity, it delivers a targeted stimulation. "So the patient is treated only when a seizure is building," explained Dr. Morrell.
The NeuroPace detects changes in frequency, amplitude, and morphology and records the time and date of these detections and the stimulations. This information is stored on an Internet-based secure server where physicians can access it, note patterns, and modify stimulations as per necessary.
"This is an iterative and dynamic process and is individualized for each patient," said Dr. Morrell.
The device battery typically lasts from 2.5 to 4 years. But because the neurotransmitter and leads are already in place, the replacement procedure is relatively short and simple, and it can be done on an outpatient basis.
The NeuroPace system is quite different from a vagus-nerve stimulator, which is also approved for the treatment of patients with epilepsy. Typically implanted in the chest, that device delivers a stimulus to the vagus nerve in the neck at set intervals. Deep-brain stimulation to the nucleus of the thalamus is not approved in the United States for the treatment of epilepsy.
During the AES meeting, Dr. Morrell and colleagues shared results of trials using the NeuroPace device. One was a 2-year feasibility trial in 65 patients who were experiencing 3 or more seizures per month. That trial was followed by a double-blind, randomized, sham-stimulation controlled pivotal trial.
The pivotal study enrolled 191 patients aged 16 to 65 years (mean age at time of implant was 34.9 years) at 32 sites across the United States. The mean duration of epilepsy among these patients was 20.5 years, the daily number of AEDs at enrollment was 2.8, and the mean number of seizures per month was 34.2.
Over the blinded evaluation period (2 to 5 months after implant), seizures were reduced by 37.9% in the treatment group (n = 97) and 17.3% in the sham group (n = 94) (P = .012).
During the open-label period of the pivotal study, the median percentage reductions in seizures compared with baseline were 43.8% at 1 year and 52.9% at 2 years after implant. The responder rates were 43.6% at 1 year and 54.6% at 2 years. This slope of improvement was significant at P < .0001, the researchers say.
The reduction in seizures with responsive stimulation was similar across patients who had changes in their AEDs (n = 98) and those who did not (n = 88). "This indicates that the favorable response to responsive stimulation was not explained by changes in antiepileptic medication therapy," said Dr. Morrell.
Patients participating in either of these trials were able to transition into a study to provide 7 additional years of follow-up. Both the median percentage reduction in seizures and the responder rate exceeded 50% at each year after implant. For example, at year 6 (months 72 to 74; n = 72), the median percentage reduction was 58.3% and the responder rate was 58.3%.
"The results of these studies show that patients continue to improve over the first 2 years of treatment, and thereafter the therapy appears to be very durable," commented Dr. Morrell.
Stimulation in most patients occurs for less than 6 minutes per day in total. Patients, said Dr. Morrell, don't seem to be aware of the implant, which is "quietly going on in the background." Unlike drug therapy, the device doesn't require patients' compliance, she noted.
Adverse events, including depression, memory impairment, and anxiety, occurred at about the same low rate in both the active treatment and sham study groups. Most events occurred in the first year after implant, and the overall rate of device-related adverse events declined with time.
Dr. Morrell noted that adverse effects did not include those often associated with AEDs, such as problems with cognition and coordination and fatigue.
All potentially serious adverse events were expected and included infection at the implant site. About 4.8% of patients had such an infection, said Dr. Morrell.
According to data in an abstract on long-term safety and efficacy of the device, 11 patients died: 2 of suicide, 1 each of status epilepticus and lymphoma, and 7 of sudden unexpected death in epilepsy (SUDEP). Two of the SUDEP decedents were not being treated with responsive stimulation. The SUDEP rate was 3.9 per 1000 patient stimulation-years.
NeuroPace is committed to carrying out postapproval studies in 300 patients over the next 7 years that will gather further safety information "in the real-world population," said Dr. Morrell.
The neurostimulator could be a treatment option for patients who have not responded to drug treatment, have 1 to 2 defined seizure foci, and are not good candidates for surgery, Dr. Morrell told Medscape Medical News.
"These are often patients who have bilateral mesial temporal onsets so they are not candidates for unilateral temporal lobectomy, or patients who have seizures beginning in functional brain," so resection would not be an option for them, she said.
Only 15% to 20% of patients with intractable epilepsy are good candidates for surgery, she noted.
Asked to comment on the new device, Dawn Eliashiv, MD, professor, neurology, and co-director, Seizure Disorder Center, University of California at Los Angeles (UCLA), said that one of its advantages is that the placement of the electrodes can be tailored to the individual.
"This is especially useful in patients in whom you've identified where the seizures are coming from but it's close to areas of language or critical motor functions, so areas that can't be resected," said Dr. Eliashiv. "Or, in some patients who have seizures coming from both sides, with the RNS, you can place 4 electrodes on each side."
Brian Moseley, MD, clinical instructor, UCLA, added, "it's absolutely excellent that we now have another tool we can offer folks" who are eligible.
Although surgery can render up to 70% of patients completely seizure free, Dr. Moseley agreed that this treatment approach is not an option for patients with seizures in areas of the brain deemed essential for function.
"Even if patients are completely seizure free, if they can't talk or they can't understand speech or can't move an essential part of the opposite side of their body the cure is worse than the disease."
Dr. Morrell is an employee of NeuroPace. The commenters have disclosed no relevant financial relationships.
American Epilepsy Society (AES) 67th Annual Meeting. Platform B.05. Presented December 7, 2013.
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Cite this: Neurostimulator Provides Long-Term Seizure Control - Medscape - Dec 11, 2013.